Duodenal eosinophilia is associated with symptomatic erosive gastro-oesophageal reflux disease, presence of co-morbidities, and ethnicity but not undifferentiated functional dyspepsia: A retrospective Malaysian study.

BACKGROUND: Duodenal eosinophilia is postulated to play a key role in the pathogenesis of functional dyspepsia, a common condition responsible for considerable impairment of quality of life. Our objective was to evaluate the relative strength of the associations between duodenal eosinophilia, functional dyspepsia, symptomatic erosive gastroesophageal reflux disease (GERD), the presence of co-morbidities, and a number of other variables. METHODS: Eosinophil counts of archived endoscopic duodenal biopsies of 289 subjects were determined by a pathologist blinded to the clinical data. Duodenal eosinophilia was defined by a count of more than 15 per 5 high power fields. Clinical charts were reviewed by a gastroenterologist blinded to the histology review. RESULTS: In the study sample, the primary diagnosis was functional dyspepsia (undifferentiated by subtypes) in 45, symptomatic erosive GERD in 29, gall stone disease in 17, irritable bowel syndrome in 23, and an alternative or undetermined diagnosis in 175 subjects, respectively. On logistic regression analyses, eosinophil counts were positively associated with symptomatic erosive GERD (Odds Ratio, OR 1.03, 95% Confidence Interval, 95%CI: 1.00, 1.05; p=0.035) but not functional dyspepsia. Pre-defined duodenal eosinophilia was associated with symptomatic erosive gastro-oesophageal reflux disease (OR 3.36, 95%CI 1.18,-9.60; p=0.023), the presence of co-morbidities (OR 2.00, 95%CI 1.10, 3.62; p=0.022), and Chinese (as compared to Malay and Indian) ethnicity but not with either functional dyspepsia, irritable bowel syndrome, gallstone disease, Helicobacter pylori infection, or gender. CONCLUSION: Duodenal eosinophilia was associated with symptomatic erosive GERD, the presence of co-morbidities, and Chinese ethnicity but not with undifferentiated functional dyspepsia.

A retrospective audit of endoscopic duodenal biopsies to uncover undetected Coeliac disease in Malaysian patients.

BACKGROUND: Coeliac disease, an autoimmune enteropathy related to gluten sensitivity was hitherto thought to be rare in Asia. Recent data however suggests that Celiac disease may be under-diagnosed in Asia. OBJECTIVE: The aim of this audit was to determine the frequency of histological changes compatible with Coeliac disease among patients undergoing elective diagnostic oesaphago-gastro-duodenoscopy (OGDS) under the care of a single practitioner in a Malaysian hospital. MATERIALS AND METHODS: The archived endoscopically obtained duodenal biopsy specimens of 241 consecutive Malaysian subjects undergoing elective diagnostic (OGDS) were reviewed by a pathologist blinded to the clinical data. Based on intra-epithelial lymphocyte counts, crypt hyperplasia and villous atrophy, each subject was assigned to one of the categories of the Modified Marsh classification for the histological diagnosis of Coeliac disease. The clinical charts of all subjects were reviewed by a single gastroenterologist blinded to the findings of the histological review. RESULTS: Of the 241 study subjects, 132 (54.8%) were females. There were 56 (23.2%) Malays, 90 (37.3%) Chinese, 88 (36.5%) Indians and seven (2.9%) from the other category. The median age of the study sample was 49 years (range 15- 88 years). The OGDS was done as part of screening in 15(6.2%) subjects while in the remaining it was part of the investigation of a clinical problem. Based on histological findings, none of the subjects could be assigned to a modified Marsh class of >1. The prevalence of histological changes compatible with Coeliac disease in the study was 0% (binomial exact one-sided 97.5 % confidence interval 0- 1.52%). CONCLUSION: In conclusion, this audit provides no evidence that active Coeliac disease is significantly under-detected among symptomatic patients presenting for diagnostic OGDS. The possibility that a significant number may have potential coeliac disease cannot be excluded.

Sociocultural and dietary practices among Malay subjects in the north-eastern region of Peninsular Malaysia: a region of low prevalence of Helicobacter pylori infection.

BACKGROUND AND AIM: The prevalence of Helicobacter pylori infection is exceptionally low among the Malays in the north-eastern region of Peninsular Malaysia. The reasons are unknown. Our aim was to compare environmental factors that differed in relation to H. pylori prevalence among Malays born and residing in Kelantan. METHODS: A case-control study was conducted among Malays in Kelantan who underwent upper endoscopy between 2000 and 2008. Helicobacter pylori status was determined by gastric histology. Sociocultural and dietary factors were assessed using a validated investigator-directed questionnaire administered after 2008, and the data were analyzed using logistic regression analysis. RESULTS: The study group consisted of 161 subjects (79 H. pylori positive and 82 controls). Univariable analysis identified five poor sanitary practices associated with an increased prevalence of H. pylori infection: use of well water, use of pit latrine, less frequent boiling of drinking water, and infrequent hand wash practice after toilet use and before meals. Multivariable logistic regression analysis identified three variables inversely associated with H. pylori infection: frequent consumption of tea (OR: 0.023, 95% CI: 0.01-0.07), frequent use of "budu" or local anchovy sauce (OR: 0.09, 95% CI: 0.1-0.7), and frequent use of "pegaga" or centenella asiatica (OR: 0.25, 95% CI: 0.1-0.65). CONCLUSIONS: Under the assumption that sanitary, sociocultural, and dietary habits have not changed over the years, we can conclude that an increased risk of H. pylori was associated with unsanitary practices whereas protection was associated with consumption of tea and locally produced foods, "pegaga" and "budu." These dietary factors are candidates for future study on the effects on H. pylori transmission.

The effect of propranolol in malay patients with liver cirrhosis - a pharmacodynamic evaluation.

The pharmacodynamics of propranolol were studied in 12 cirrhotic Malay patients. Fifteen healthy Malay volunteers were selected and several clinical parameters were obtained. The effects of three doses of propranolol in reducing the heart rate (HR) of these patients were observed to be significantly different. These differences were seen at dosing of 10 mg vs 20 mg and 10 mg vs 30 mg (P<0.001 and P<0.01, respectively). However, no significant difference was seen for doses between 20 mg vs 30 mg. At 20 mg the reduction in HR is more pronounced than the effect seen with the other two doses. The effects of propranolol in reducing V(max) and V(mean) of portal vein blood flow were found to be not significant at doses of 10 mg vs 30 mg, but between 10 mg vs 20 mg and 20 mg vs 30 mg there was significant difference (P<0.05 and P<0.01, respectively). Reduction of V(max) of more than 10% of baseline was achieved at doses of 10 mg and 20 mg. However, at a dose of 20 mg a more significant reduction was observed than at a dose of 10 mg. Dose-concentration-effect relationship was seen to be significantly different between HR reduction and propranolol concentration of the three steady-state levels (P<0.001). Similar results were obtained with V(max) and V(mean). The V(max) was found to be a reliable parameter for the assessment of therapeutic effect of the drugs in conferring changes in portal haemodynamics of liver cirrhotic patients. Further, Child-Pugh score is thought to be an important supporting factor in evaluating prognosis. The results of this pharmacodynamics studies suggest that the optimal dose of propranolol may be 20 mg propranolol thrice daily for cirrhotic Malay patients.

The Pharmacokinetics of Single Dose vs Steady-State Doses of Propranolol in Cirrhotic Malay Patients.

Pharmacokinetics of propranolol (PRN) given orally were studied in twelve cirrhotic Malay patients [10 males, 2 females], aged 33-62 years [49.83±9.17], body weight 39-72 kg [58.0±8.46] and height 142-168 cm [158.8±7.89] following single 20 mg and steady-state 20 mg tds for 7 days dosing of PRN. Blood samples were withdrawn hourly up to 48 hours. PRN concentrations in the plasma were assayed by HPLC with oxprenolol as the internal standard. Pharmacokinetic parameters were analysed using a non-linear regression program MultiForte. Area under the curve (AUC) as performed using the linear trapezoidal rule. Student's t-test was used to test for statistical significance and AUC in Malay cirrhotic patients was found to be much bigger than that observed in Caucasians. Steady-state AUC was significantly increased following multiple dosing (961.31±7.47 vs 2954.19±1153.34 ng.hr/ml), however, the volume of distribution (V(d)) declined (543.89±292.91 vs 224.14±1003.12 L) significantly compared to that of a single dose. The apparent systemic clearance (CL) was significantly reduced at steady-state (436.04±209.4 vs 129.51±48.42 ml/min) in comparison to single dose therapy. The peak plasma concentration (Cp(max)) was greatly increased at steady-state (54.32±22.37 vs 136.10±38.63 ng/ml). Based on the AUC, PRN bioavailability was greater in cirrhotic Malay patients compared to Caucasians who took only 20 mg instead of 80 mg doses. The decline in drug clearance following steady-state was due to saturation of the metabolizing capacity of hepatic enzymes and a decreased portal blood flow. Reduced V(d) was believed to be caused by increased drug-receptor interactions and decreased tissue/protein binding of PRN in these patients.

Trichuris Dysentery Syndrome: evidence that it may be underdiagnosed in Kelantan.

The prevalence rate of trichuriasis in children in certain areas of Kelantan is high. However the Trichuris Dysentery Syndrome (TDS), a condition in children characterized by chronic diarrhoea, stunting and anaemia is said to be rare. A recent change in policy at our institution to lower the threshold for undertaking colonoscopy in children with chronic diarrhoea resulted in the detection of 6 cases of TDS in less than a year. The median age was 7 years (range 3-13) and the median duration of symptoms before diagnosis was 2 years (range 1-8). The insidious nature of TDS and the low level of awareness of this condition even among health care workers may result in considerable underdiagnosis.

Intestinal geohelminthiasis and growth in pre-adolescent primary school children in Northeastern Peninsular Malaysia.

A cohort of one hundred 8-9 year old school children in Northeastern Peninsular Malaysia underwent stool examination, weight and height measurements. Seventy-three children were infected with Ascaris lumbricoides and/or Trichuris trichiura. All infected children were treated with albendazole at baseline, 6 months and 9 months. Measurements were repeated on all but 2 children at 1 year. Repeat stool examination (n = 94) at 1 year revealed a marked reduction in the level of Ascaris infection and a modest reduction in Trichuris infection. There was no difference in net growth between treated children and uninfected controls. Post-hoc analysis by gender however revealed that infected girls (n = 33) experienced significantly higher increments in weight, height and weight for age. Furthermore, children found to be infected at baseline level but worm free at follow-up, were observed to have experienced greater increments in height and height for age. The evidence suggests that periodic antihelminthic treatment may have a positive effect on the growth of subsets of pre-adolescent children but it is emphasised that further work is required to validate these findings.

Management of Helicobacter pylori infection--a Working Party Report of the Malaysian Society of Gastroenterology and Hepatology.

The Working Party Report on the Management of Helicobacter pylori serves as a clinical practice guideline for Malaysian doctors. H. pylori is not uncommon in the Malaysian population. Marked racial differences and the consistently low prevalence rates amongst Malays are noted. The working party recommends that if endoscopy is to be performed, a rapid urease test should be used for diagnosis. Where suspicion of the infection is strong and the urease test is negative, histology should be performed on gastric biopsies. Culture should be used to monitor resistance patterns to antibiotics and regional laboratories should assume this responsibility. The urea breath tests are highly accurate tests for diagnosis of H. pylori but is as yet not widely available in Malaysia. The working party strongly recommends that all peptic ulcer patients infected with H. pylori whether active, in remission and complicated ulcers should be treated for the infection. Patients with low-grade gastric mucosal lymphoid tissue lymphoma should also be treated for H. pylori infection. It is considered advisable that patients on long term nonsteroidal antinflammatory drug (NSAID) treatment with a history of peptic ulcers or dyspepsia and patients following resection of early gastric cancer or those with a family history of gastric cancer should also be tested and treated for H. pylori. The working party recommends, as first line treatment a 7-day combination therapy of a proton pump inhibitor, clarithromycin and metronidazole or amoxicillin. High metronidazole resistance rates locally may adversely affect regimens containing the antibiotic. It should also be noted that regimens that yield lower eradication rates may result in higher long term expenditure.

Intestinal helminthiasis in relation to height and weight of early primary school children in northeastern peninsular Malaysia.

Stool examination, height and weight measurements were undertaken on 249 early primary school children at two schools in North-eastern Peninsular Malaysia. Helminth infected children were treated and follow-up anthropometric measurements and stool examination undertaken on all (n = 100) children at one of the schools 16 months later; to observe the relationship between acquisition of infection and growth. Baseline Ascaris prevalence rates at the two schools were 16.0% (23/144) and 47.6% (50/105) respectively whilst Trichuris rates were 33.3% (48/144) and 52.4% (55/105). Hookworm infection was uncommon. There was no difference in weight or height for age between infected and uninfected children at any time. Acquisition of worm infection over the initial 16 month follow-up period was not associated with significant decreases in growth rates. However the small subsets of children with heavy Ascaris infection were consistently lighter and shorter at all evaluation times. They also gained significantly less weight and tended to have reduced linear growth rates between measurements. Further interventional studies are required to determine if this association is one of cause and effect or largely incidental.

Left ventricular outflow tract (LVOT) vegetations and spontaneous obliteration of a large ruptured intracranial mycotic aneurysm in a case of infective endocarditis.

A 10-year-old girl with mild aortic regurgitation presented with cerebral infarction. Two-dimensional echocardiography showed vegetations on the septal wall of the left ventricular outflow tract without involvement of the aortic valve itself. After successful antibiotic treatment the patient developed an intra-cranial haemorrhage due to rupture of a large intracranial mycotic aneurysm. Consent for surgical treatment of the mycotic aneurysm was not obtained. Twelve months later repeat angiography showed that the aneurysm had undergone spontaneous obliteration.

Intestinal helminthiasis and abdominal symptoms in adults.

In a study to test the association between soil transmitted intestinal helminthiasis and abdominal symptoms in a non-paediatric age group, 242 randomly selected patients (137 males, 105 females, median age 45 years) were asked specific questions pertaining to abdominal symptoms at the time of admission to the adult medical wards. Stool examination on all patients revealed a round worm prevalence rate of 21%. A larger proportion of stool positive female patients were symptomatic than stool negative females (68% vs 30%, p = 0.04). There was no significant difference in symptoms between stool positive and stool negative male patients (34.6% vs 31%, p = 0.91). The results suggested an association between intestinal nematode infection and abdominal symptoms in females but not in males.